1. Field of the Invention
The invention relates to a method of manufacturing 1-chloro-2-methyl-4-acyloxy-2-butene derivatives, which are important precursors of Vitamin A acetate.
2. Description of the Related Art
Vitamin A and its derivatives are used in great quantities as medicines, food additives and feed additives. One of the most important Vitamin A derivatives is Vitamin A acetate. The key intermediate in the C15+C5 Wittig-based synthesis of Vitamin A acetate is 4-acetyloxy-2-methyl-2-butene-1-aldehyde (a C5 aldehyde of MW 142) (Tanaka, U.S. Pat. No. 5,424,478, Process for producing Vitamin A Derivatives, [P] 1995; Tanaka, et al., JP Pat. No. 06,329,623, Preparation of Vitamin A Derivatives, [P] 1994; Zutter, Ulrich, EP 648,735, Preparation of an intermediate for Vitamin A acetate, [P] 1995).

Since H. Pommer at BASF reported an industrial scale synthesis of the C5 aldehyde (H. Pommer, A. Nurrenbach, Pure. Appl. Chem., Industrial synthesis of Terpene compounds, [J] 1975, 43, 527), there has been no shortage of improvements. Among them, use 1-chloro-2-methyl-4-acetyloxy-2-butene to prepare the C5 aldehyde is well documented (Tanaka, et al., JP Pat. 06,329,623, Preparation of Vitamin A Derivatives, [P] 1994; Ven Kataratnam, Revannuru V., et al., IN Pat. IN 168,539, An improved process for the preparation of 4-acetoxy-2-methyl-2-butenal, [P] 1988; Kaneko, Tatsuhiko, et al., JP 07,61,948, Preparation of α,β-unsaturated aldehydes, [P] 1995; Babler, James. H., PCT. Int. Appl. 7900,485, E-4-Acetoxy-2-methyl-2-butenal, [P] 1979; Babler, James H., U.S. Pat. No. 4,175,204, E-4-Acetoxy-2-methyl-2-butenal, [P] 1979; Babler, James H., J. Org. Chem., Facile synthesis of 4-acetoxy-2-methyl-2-butenal, a Vitamin A precursor [J] 1979, 44(10), 1716-17). This it is safe to say that 1-chloro-2-methyl-4-acetyloxy-2-butene is an important intermediate in the synthesis of Vitamin A acetate.
When methyl is replaced by a different alkyl in the first equation below, it yields important intermediates for the synthesis of various other Vitamin A derivatives.

There are two main methods to prepare 1-chloro-2-methyl-4-acyloxy-2-butene derivatives. The first method by Babler uses chloroacetone as raw material, which is first reacted with a vinyl Girgnard to yield a tertiary alcohol intermediate which then undergoes esterification and rearrangement to yield 1-chloro-2-methyl-4-acyloxy-2-butene derivatives, as follows (Babler, James. H., PCT. Int. Appl. 7900,485, E-4-Acetoxy-2-methyl-2-butenal, [P] 1979; Babler, James. H., U.S. Pat. No. 4,175,204, E-4-Acetoxy-2-methyl-2-butenal, [P] 1979; Babler, James. H., J. Org. Chem., Facile synthesis of 4-acetoxy-2-methyl-2-butenal, a Vitamin A precursor [J] 1979, 44(10), 1716-17).

The second method uses isoprene as raw material, which reacts with sodium hypochlorite in a chlorohydrins formation reaction to yield a mixture of 1,2 and 1,4 addition products. The mixture then undergoes esterification and rearrangement to yield 1-chloro-2-methyl-4-acyloxy-2-butene (Tanaka, et al., JP 06,329,623, Preparation of Vitamin A Derivatives, [P] 1994; Kuroda, Noritaka, et al., JP. 06,345,689, Preparation of butenal derivatives, [P] 1994).

The second method is potentially more valuable industrially because of its low cost and facile process conditions. For example, to maintain the pH during the chlorohydrin reaction, CO2, H2SO4, HCl or CH3COOH can be added. However, we have found through experiments that the content of the product in this process is low and the yield is low as well.
Ordinarily, olefin chlorohydrin formation reaction can be realized by adding chlorine to an aqueous suspension of calcium hydroxide, making use of the active hypochlorous acid formed. However, we have found through experiments that the content of products obtained in this process is low, perhaps owing to the fact that the existence of free chlorine and other heteroions provokes a side reaction of the olefin's double bond, such as a dichloroaddition, etc. This increases impurities.
Therefore, it is presumed that the chlorohydrin reaction can be modified by proceeding in a more mild system, which contains fewer heteroions. N-chloroisocyanuric acid series compounds (comprising trichloroisocyanuric acid A, dichloroisocyanuric acid B, a sodium salt of dichloroisocyanuric acid C, and a potassium salt of dichloroisocyanuric acid D, or other metal-salts thereof, dichloroisocyanuric acid sodium salt contained crystal water, monochloroisocyanuric acid and its metal-salt etc.; or complexes made up of two or more compounds mentioned above) widely serve as detergents, cleaning agents, bactericidal and sanitizing compounds of public use and domestics. At present, this series compound begins to find use in organic chemistry.
Structural formula of several main kinds of N-chloro-isocyanuric acid series compounds are illustrated below:

Among these are, trichloroisocyanuric acid (A) (trichlorotriazinetriketone, molecular formula: Cl3(CNO)3, the content of available chlorine about 90%) which has the highest content of available chlorine in all solid matter, organic and inorganic alike; sodium salt of dichloroisocyanuric acid (C) (molecular formula: NaCl2(CNO)3, the content of available chlorine about 62.5%); and its crystal water form (molecular formula: NaCl2(CNO)3.2H2O, the content of available chlorine about 55.5%), all commonly and widely used.
The N-chloroisocyanuric acid derivatives can react with water and generate hypochloric acid and corresponding derivatives of cyanuric acid. For example of trichloroisocyanuric acid reacts with water as follows:

This reaction is rapid and thorough, and all the available chlorine can be made full use of.
Accordingly, we have tried our best to make use of the N-chloroisocyanuric acid series of compounds in place of sodium hypochlorite and calcium hypochlorite which have been mentioned above in the chlorohydrin formation reaction. We have discovered during these endeavors that content of the desired product in the reaction mixture and the yield improved greatly and the amount of waste reduced enormously, both of which demonstrate a great industrial value to these reagents.